Baggott J E, Vaughn W H, Juliana M M, Eto I, Krumdieck C L, Grubbs C J
Department of Nutrition Sciences, University of Alabama, Birmingham 35294-3360.
J Natl Cancer Inst. 1992 Nov 18;84(22):1740-4. doi: 10.1093/jnci/84.22.1740.
There are metabolic and epidemiologic data consistent with the hypothesis that folate deficiency increases the likelihood of cancer. Conversely, it is also known that folate is necessary for cancer growth, but few experiments in laboratory animals have evaluated the effects of folate deficiency on the development of chemically induced cancers.
Our purpose was to determine the effects of nutritional folate deficiency in female Fischer 344 rats on initiation and early promotion of methylnitrosourea (MNU)-induced mammary cancer.
Rats (age, 27 days) were fed a folic acid-deficient diet (AIN-76A) supplemented with glycine and succinylsulfathiazole [FA(0)]; the FA(0) diet supplemented with 2 or 40 mg of folic acid per kilogram [FA(2) or FA(40), respectively]; or the FA(0) diet supplemented with 20 mg of folinic acid per kilogram [FL(20)]. At 57 days of age, each diet-treated group (30 rats in each group) received MNU (50 mg/kg) by intravenous injection. Immediately after MNU treatment, all animals were fed the AIN-76A complete diet containing 2 mg of folic acid per kilogram. Control groups were fed the AIN-76A complete diet throughout the entire experiment.
After 4 weeks, folate deficiency, but not anemia or growth suppression, was documented by lower folate levels in plasma and red blood cells in the group receiving the FA(0) diet. Cancer multiplicity (i.e., number of mammary cancers per number of tumor-bearing animals) at 180 days after MNU injection was 1.32, 1.90, 2.14, and 2.73 mammary cancers per tumor-bearing animal in the FA(0), FA(2), FA(40), and FL(20) groups, respectively; the value in the FA(0) group was statistically significant compared with the values in the other groups. The time required for 50% of the rats to develop palpable mammary cancer was 170, 142, 100, and 85 days, respectively. The value of 170 days for the FA(0) group was statistically significant compared with the values of 100 and 85 days. Mammary cancer incidence was 63%, 70%, 72%, and 73%, respectively; these percentages were not significantly different.
Folate deficiency suppresses and folate supplementation enhances initiation or early promotion of MNU-induced mammary cancer in rats, even when the folate-deficient rats do not have anemia or growth suppression.
Since the rat is relatively resistant to folate deficiency anemia, other animal models should be used to test the effect of folate nutriture on carcinogenesis.
有代谢和流行病学数据支持叶酸缺乏会增加患癌可能性这一假说。相反，已知叶酸对癌症生长是必需的，但在实验动物中很少有实验评估叶酸缺乏对化学诱导癌症发生发展的影响。
我们的目的是确定雌性Fischer 344大鼠营养性叶酸缺乏对甲基亚硝基脲（MNU）诱导的乳腺癌起始和早期促进的影响。
将大鼠（27日龄）喂食添加甘氨酸和琥珀酰磺胺噻唑的叶酸缺乏饮食（AIN - 76A）[FA(0)]；分别在FA(0)饮食中添加每千克2毫克或40毫克叶酸[分别为FA(2)或FA(40)]；或在FA(0)饮食中添加每千克20毫克亚叶酸[FL(20)]。57日龄时，每个饮食处理组（每组30只大鼠）通过静脉注射接受MNU（50毫克/千克）。MNU处理后立即给所有动物喂食含每千克2毫克叶酸的AIN - 76A完全饮食。对照组在整个实验过程中喂食AIN - 76A完全饮食。
4周后，接受FA(0)饮食组血浆和红细胞中叶酸水平降低，证明存在叶酸缺乏，但无贫血或生长抑制。MNU注射后180天，FA(0)、FA(2)、FA(40)和FL(20)组每只荷瘤动物的乳腺癌多发性（即每只荷瘤动物的乳腺癌数量）分别为1.32、1.90、2.14和2.73个乳腺癌；FA(0)组的值与其他组相比具有统计学意义。50%的大鼠出现可触及乳腺癌所需时间分别为170、142、100和85天。FA(0)组170天的值与100天和85天的值相比具有统计学意义。乳腺癌发病率分别为63%、70%、72%和73%；这些百分比无显著差异。
叶酸缺乏会抑制，而叶酸补充会增强大鼠中MNU诱导的乳腺癌的起始或早期促进，即使叶酸缺乏的大鼠没有贫血或生长抑制。
由于大鼠对叶酸缺乏性贫血相对有抵抗力，应使用其他动物模型来测试叶酸营养状态对致癌作用的影响。
